Meet a Microbiome Researcher — Dr. Christopher J. Stewart

Dr. Stewart discusses characterization of the microbiome of neonates and infants in relation to health and disease

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Dr. Christopher Stewart completed his Ph.D. at Northumbria University Newcastle upon Tyne in 2014 and later moved to the United States for his postdoctoral training. He is currently a Postdoctoral Researcher at Baylor College of Medicine (Houston, TX). His research interests are focused on the diversity and ecology of microbial communities and host responses in clinical samples and ex vivo model systems to determine the microbial-host interaction in health and disease.

Dr. Stewart's work has used molecular, culture, proteomic and metabolomic techniques to explore a range of clinical samples, primarily from early life. He ran a molecular sequencing and mass spectrometry lab, developing and optimizing novel mass spectrometry methods for profiling the proteome and metabolome of clinical samples. He has extensive experience in bioinformatics and statistical analysis of complex multi-omic datasets. He has also developed a novel ex vivo co-culture system using human resected tissue (enteroids) that allows validation of clinical experiments and aids mechanistic understanding. The ultimate goal of his research is centered on elucidating the mechanisms of pathogenesis and potential biomarker discovery for a range of disease states.

We interviewed Dr. Stewart to discuss characterization of the microbiome of neonates and infants in relation to health and disease.

Tell us about your background. How did you get interested in science? Did you always want to work in the microbiome field?

Throughout my childhood and into my teen years I played football (soccer) for Newcastle United and hadn’t really considered being anything other than a professional footballer. It wasn’t until my mid-to-late teens I realized I needed an alternative career path. I was fortunate to have encouraging science teachers during high school and coupled with my interest in informatics, I went on to study Biotechnology at university. During the final year of my undergraduate studies I carried out a microbial ecology wet-lab project under the supervision of Professor Stephen Cummings. For the first time in my life I was not going into a pre-prepared lab to perform work with a known outcome. We were testing and optimizing methods, exploring something that had never been explored before and with no guarantee of success – it was proper science and I loved it!

Can you give a summary of the project that won the microbiome award and any updates on the work since the award was issued?

My project aimed to determine the longitudinal development of the preterm gut microbiome throughout neonatal intensive care and into childhood, representing an extension to my study in Nature Scientific Reports. Due to the relative ease in collecting samples while babies are in intensive care, most studies have focused on this neonatal stage of life. I wanted to look further and determine how the microbiome continues to develop once the infants leave intensive care and what influences this may have on the health of the infant. The first year of life likely represents the key window of opportunity for ‘seeding’ a beneficial microbiome to maximize an individual’s overall wellbeing. Thus, better understanding of the microbiome during this key window is imperative to the development of therapeutics such as probiotics. At this stage of the project, we have acquired all samples, which is always tricky when requesting parents collect and post samples to the lab. I hope to have the sequence data in the coming weeks and I’m excited to see what we find!

Are you working on any other new projects in the field of microbiome research? If so can you tell us a little about these?

I moved from the U.K. to Baylor College of Medicine (Houston, TX) around 18 months ago and since joining the lab of Professor Joseph Petrosino I have had some amazing opportunities to continue my research on the development of the microbiome in early life. I have continued my research in preterm infants, more recently focusing on developing a novel and clinically relevant ex vivo model for validating the associations discovered in microbiome experiments. Away from the wet-lab, I perform bioinformatics on multi-omic datasets, for which I am currently working on the unprecedented TEDDY cohort and the MARC-35 (in collaboration with Drs. Camargo, Mansbach and Hasegawa at Harvard Medical School) to determine what factors influence the early life microbiome and how this influences the risk of Type 1 diabetes or respiratory disease in childhood, respectively.

What do you find most interesting about your project? What is the most interesting or surprising result you have found?

Because my work typically involves the use of clinical samples collected from human patients, it is very exciting and rewarding to be at the interface between the bench and bedside. Indeed, there is huge potential for translating microbiome research into clinical practice and we are seeing that with the emergence of probiotics and fecal microbiome transplants in a range of diseases. I think the most surprising result to me is my recent finding that the microbiome in preterm infants might protect the infant from severe gastrointestinal disease, rather than cause disease. Thinking back to the beginning of my Ph.D., before microbiome research truly emerged to the level it’s at today, I (perhaps naively) thought that I would find the ‘smoking gun’ in disease causing bacteria. My recent publication in the journal Microbiome, as well as the data of others, has shifted my mindset away from the presence of certain bacteria causing disease toward thinking certain bacteria may protect from disease and a lack of these beneficial microbes increases disease risk. We very rarely find consistency in the bacteria deemed to cause disease between studies (even separate studies within the same site), but there is more commonality in bacterial species associated with controls (healthy individuals). Clearly, there is more at play than simply which bacteria reside in a given niche, and the prospect of tailoring ones’ microbiome to promote stability and host maturation has important connotations in personal medicine, especially for vulnerable preterm infants.

What are the important benefits of your research to science and human or animal health?

My research, along with others in the field, has extensively characterised the gut microbiome in early life and how temporal changes in development may increase disease risk or promote health. With the recent addition of functional data to complement my microbiome data, such as metabolomics and proteomics, I am beginning to determine the consequential changes in the microbiome on host functioning. Together, these data will provide 1) novel information on disease pathogenesis, 2) biomarkers to predict and detect disease and 3) a basis for candidate organisms in probiotic therapeutic development.

Which MO BIO or QIAGEN products do you use/have you used in the past and what did you like about the products?

I have used numerous MO BIO extraction kits and during some of my early viability research I worked with Dr. Suzanne Kennedy (previous R&D at MO BIO) to help develop and test the now RNeasy PowerMicrobiome Kit. For my day-to-day microbiome studies that require DNA extraction from a range of sample types, including human and animal fecal, saliva and swab samples, I use the [now] DNeasy PowerLyzer PowerSoil Kit. Working with Dr. Heather Callahan (R&D) I also recently tested the NoviPure and AllPrep Bacterial DNA/RNA/Protein Kit on human stool samples. The microbiome profiles from the DNA extractions look great and my protein samples are currently with proteomics core for mass spectrometry. Kits like the AllPrep Kit will be a great asset to my multi-omic experiments, where from a single extraction I can obtain high-quality DNA and protein, allowing 16S rRNA sequencing as well as host proteomic and meta-proteomic profiling data to be obtained.